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      Dangerous unmarked genes

      Nature Reviews Cancer
      Springer Nature America, Inc

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          Global loss of imprinting leads to widespread tumorigenesis in adult mice.

          Loss of imprinting (LOI), commonly observed in human tumors, refers to loss of monoallelic gene regulation normally conferred by parent-of-origin-specific DNA methylation. To test the function of LOI in tumorigenesis, we developed a model by using transient demethylation to generate imprint-free mouse embryonic stem cells (IF-ES cells). Embryonic fibroblasts derived from IF-ES cells (IF-MEFs) display TGFbeta resistance and reduced p19 and p53 expression and form tumors in SCID mice. IF-MEFs exhibit spontaneous immortalization and cooperate with H-Ras in cellular transformation. Chimeric animals derived from IF-ES cells develop multiple tumors arising from the injected IF-ES cells within 12 months. These data demonstrate that LOI alone can predispose cells to tumorigenesis and identify a pathway through which immortality conferred by LOI lowers the threshold for transformation.
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            Author and article information

            Journal
            Nature Reviews Cancer
            Nat Rev Cancer
            Springer Nature America, Inc
            1474-175X
            1474-1768
            December 2005
            November 18 2005
            December 2005
            : 5
            : 12
            : 914
            Article
            10.1038/nrc1767
            cd116e4e-94b4-4619-8a37-4f01877003d7
            © 2005

            http://www.springer.com/tdm

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